1. www.global-campaign.org Access to Care and Treatment in Microbicide Trials: Findings from the SOC Mapping Exercise Sean Philpott, PhD, MSBioethics Science and Ethics Officer Consultation on Operationalizing Access to HIV Treatment and Care June 19th, 2008

2. www.global-campaign.org Standard of Care The concept of standard of care is rooted in the physician’s obligation to provide patients with the best possible care. –Boundary between expected standards of practice and medical negligence. Over the past 15 years, the concept of standard of care has migrated into the general discourse of research ethics.

3. www.global-campaign.org Standard of Care (2) Standard of care within a research context is an ambiguous and problematic concept. Ambiguity. –Meaning (a): what is routinely done: “standard practice” –Meaning (b): what ought to be done: “a standard that should be attained”

4. www.global-campaign.org Standard of Care (3) ‘Standard practice’ has never been well-defined in medicine. Standards of care can vary within and between developed and developing countries according to: –Provider knowledge, comfort, training and belief; –Local resources and context; and –Ability of the patient to pay.

5. www.global-campaign.org Standard of Care (4) What standard of care should be assured individuals who participate in HIV prevention trials? –What HIV prevention package should be provided to the control group? –What should be provided to participants who acquire the HIV during the trial? –What should be provided to participants who become ill with a disease other than that being studied?

6. www.global-campaign.org SOC Mapping Exercise: Genesis Despite lengthy debates, it was felt that information on how researchers and sites were addressing in different countries and contexts was limited. It was also felt that empiric evidence from the field could inform discussion among all stakeholders on trial ethics, as well as generate ideas for future trial design.

7. www.global-campaign.org SOC Mapping Exercise: Goals Document progress made by researchers toward meeting ethical guidance and aspirations; Compare context-specific challenges in provision of care and prevention; and Describe different SOC strategies and how sites implemented them.

8. www.global-campaign.org SOC Mapping Exercise: Methods Development of survey guide with input from investigators and staff; Desk review of 7 study protocols & international and site-level documents (SOPs, manuals); In depth interviews with international investigators and sponsors; Visits to a sample of 6 sites and community clinical facilities in 4 countries; In-depth interviews with site trial staff; and Consultation in Johannesburg, SA.

9. Sites included SiteTrialProduct 1. Gugulethu, SA 2. Shoshanguve, SA Population CouncilCarraguard 3. Cotonou, BeninCONRADCellulose sulfate 4. KwaZulu Natal, SA 5. Mwanza, Tanzania Microbicides Development Program Pro2000 Gel 6. Harare, ZimbabweHIV Prevention Trials Network MIRA BufferGel & Pro2000 Gel Diaphragm 7. Nigeria and Ghana (* NOT VISITED) Family Health International Savvy in Ghana Cellulose sulfate in Nigeria

12. www.global-campaign.org SOC Mapping Exercise: Range of Issues Examined HIV risk reduction STI services Cervical screening Contraception Pregnancy Research-related harms Care for Seroconverters Care of HIV+ Screen-outs Continuity of care Capacity building Ancillary care

13. www.global-campaign.org SOC Mapping Exercise: Variations in Services What services were provided: –Study-related care only. –Provision of other non study-related care (primary health care). Who services were for: –Participants only. –Partners and family members of participants; Screened out women. Where services were provided: –On site. –Using different referral mechanisms.

14. www.global-campaign.org SOC Mapping Exercise: Care for Seroconverters All but one trial allowed women to continue in study and receive study related care. At a minimum, all trials provided ‘assisted referrals’ to public HIV care services, but the level of assistance varied.

15. www.global-campaign.org SOC Mapping Exercise: Care for Seroconverters (2) Some trials also offered: –WHO clinical staging; and –Baseline lab evaluations (CD4, LFTs). Only one study actually provided funds up front to pay for ART if and when needed in the future.

16. www.global-campaign.org SOC Mapping Exercise: Care for Screen-Outs All staff interviewed were increasingly concerned and responsive to need for services for women screened out All trials offered extra post-test counseling and referral. All trials provided STI screening and treatment to the woman. Most provided it to her partner.

17. www.global-campaign.org SOC Mapping Exercise: Care for Screen-Outs (2) Some trials also provided WHO staging and CD4 counts. One trial provided an on-site positive- living support group. One trial provided the same level care (including ART) to everyone. –Seoconverting participants; –Screen-outs; and –The broader community.

18. www.global-campaign.org SOC Mapping Exercise: Examples of Different Strategies CONRAD (Benin) –Complete HIV/AIDS care to all, including ART, regardless of study participation. –Post-trial ART for seroconverters funded before study began. MIRA (Zimbabwe) –Referral to public clinics for HIV care and treatment, with system to track access. –Some ARTs provided during trial. –Implemented a SOC study to look at referral process and barriers to access.

19. www.global-campaign.org SOC Mapping Exercise: Examples of Different Strategies (2) Population Council (SA) –Referral to public clinics for HIV care and treatment. At some sites, this relationship was formalized. –Each site also given a discretionary $100K budget. Gugulethu: Additional HIV care clinic. Shoshanguve: Positive-living support group. –SOC study to look at access.

20. www.global-campaign.org SOC Mapping Exercise: Examples of Different Strategies MDP (SA) –Research clinics co-located with public services. –Also benefits from the research center having a separate PEPFAR-funded ARV program. MDP (Tanzania) –Mobile clinics for high-risk women. –Women referred without assistance to local services (although monitoring of access and uptake now takes place).

21. www.global-campaign.org Donor-Imposed Obligations and Restrictions There are few donor policies that clearly establish the minimum level of prevention and care services that should be made available to all research participants. Some donors place restrictions on the use of research funds for the provision of non-trial related services, prohibit the use of resources for ancillary care and post-trial care and treatment.

22. www.global-campaign.org Donor-Imposed Obligations and Restrictions (2) National Institutes of Health (NIH) “The NIH's authority to ‘encourage and support research’ does not extend to providing treatment following the completion of that research.” (42 USC 284). Nevertheless, some funded applications must include plans for post-trial access to treatment. − E.g., NIH Guidance for Addressing the Provision of ART for Trial Participants Following Their Completion of NIH-funded HIV ART Trials in Developing Countries

23. www.global-campaign.org Donor-Imposed Obligations and Restrictions (3) Medical Research Council (MRC) Will only choose sites where infrastructure exists to complement study concerning ART and care. Participants identified as HIV infected at enrolment or during study will be referred to local structures.

24. www.global-campaign.org Donor-Imposed Obligations and Restrictions (4) Agence Nationale de Recherche sur le Sida (ANRS) Commitment that trial participants will receive treatment and care (also for illnesses that may not be focus of trial). National country programs will provide ART when required. People becoming HIV infected during trials must be eligible for ART through national programs; if this is not assured, trial will not be funded by ANRS.

25. www.global-campaign.org SOC Mapping Exercise: Key Observations The sites most successful at providing long-term access to comprehensive HIV care: –Allocated resources for HIV care and treatment from the start; –Formed working partnerships with government; and –Co-located research clinics with existing public health facilities.

26. www.global-campaign.org SOC Mapping Exercise: Site-Level Challenges to Providing Care Weak referral mechanisms; Fragile public health systems; Stigma and/or transport issues; Lack of established partnerships to provide care; and Remote location of some trial sites. –Co-location with other facilities vs. Stand-alone or mobile clinics.

27. www.global-campaign.org SOC Mapping Exercise: Broader Challenges to Providing Care Uncertainty about: 1.The ethical obligation of researchers; 2.The expectations and/or restrictions imposed by donors; 3.The meaning of “standard”; and 4.The feasibility of providing long-term access to standard care.

28. www.global-campaign.org Acknowledgments Lori Heise. Kathy Shapiro. Katie West. Trial network and research site staff. USAID.